Microvascular (capillary) bleeding is a significant source of blood loss in many conditions including bleeding liver surfaces, skin graft donor sites, inflamed visceral surfaces, and burns. Because of the diffuse nature of this type of bleeding, vessel ligation or electrocautery is not a feasible method of hemostasis. Currently, the dominant method of treatment of this type of bleeding is topical thrombin and direct pressure applied to the bleeding surface.
However, during traumatic cerebral, retroperitoneal, and pelvic hemorrhage, surgical exposure of microvascular bleeding sites can actually worsen the hemorrhage, making topical agents undesirable. Additionally, bovine antithrombin antibodies have been reported in many postoperative patients receiving topical thrombin intraoperatively causing prolongation of prothrombin time, activated partial thromboplastin time, and thrombin time up to 12-fold, as reported by Flaherty, M. J. and Wener, M. H. Antibodies to thrombin in postsurgical patients. Blood 73(5): 1386 (1989); Stricker, R. B., et al., Development of antithrombin antibodies following surgery in patients with prosthetic cardiac valves. Blood 72(4): 1375 (1988); Flaherty, M. J., et al. Iatrogenic immunization with bovine thrombin: A mechanism for prolonged thrombin times after surgery. Ann. Int. Med. 111: 631 (1989).
It is not possible to administer thrombin systemically since this could clearly result in massive systemic clotting.
It is therefore an object of the present invention to provide an alternative therapy for microvascular bleeding.
It is a further object of the present invention to provide a therapy which can be administered systemically or topically.